Patent FR-2799461-A1 (FR)
Title: Five-membered heterocycles having monoamine oxidase inhibiting, lipidic peroxidation inhibiting and sodium channel modulating activity for the treatment of e.g. central and peripheral nervous disorders
Inventor: CHABRIER DE LASSAUNIERE PIERRE
IPC: C07D409/06
Filed: 1999-10-11
Abstract: Five-membered heterocycles (III) in racemic or enantiomeric form, and their mixtures and their salts are new.  Five-membered heterocycles of formula (III) in racemic or enantiomeric form, and their mixtures and their salts are new: Het  = 5-membered heterocycle with 2 heteroatoms, such that (III) is of formula (IIIa) - (IIId); A = alkyl, cycloalkyl, cycloalkylalkyl or a group of formula (A1), (A2), (A3), (A4) or (A5); R<3> = H, OH, alkoxy, or alkyl; R<4> - R<8> = H, halogen, OH, alkyl, alkoxy, CN, NO2, or NR<10>R<11>; R<10> and R<1> = H, alkyl, or -COR<12>, or together with the N atom they form a 4-7 membered heterocycle with 1-3 heteroatoms; R<12> = H, alkyl, alkoxy or NR<13>R<14>; R<13> and R<14>  = H, alkyl; or R<13> and R<14> together with N atom = 4-7 membered heterocycle with 1-3 heteroatoms; R<9> = H, alkyl, or -COR<15>; R<15> = H, alkyl, alkoxy, or -NR<16>R<17>; R<16> and R<17> = H, alkyl, or together with the N atom they form a 4-7 membered heterocycle with 1-3 heteroatoms; W' is either not present or it  = a bond, -O-, -S-, or -NR<18>-; R<18> = H or alkyl; Q = H, -OR<22>, -SR<22>, -NR<23>R<24>, phenyl (optionally substituted by halogen, OH, CN, NO2, alkyl, alkoxy, -NR<10>R<11>, methylene dioxy or ethylene dioxy), or -COPh, -SO2Ph, -CH2Ph (these being optionally substituted on the aromatic ring by alkyl, alkoxy or halogen); R<22> = H, alkyl, or aryl (optionally substituted by alkyl, OH, halogen, NO2, or alkoxy); R<23> and R<24> = H, alkyl, or -COR<25>; R<25> = alkyl; R<19>, R<20> and R<21>  = H, halogen, OH, -SR<26>, alkyl, cycloalkyl, alkenyl, alkoxy, CN, NO2, -SO2-NHR<49>, -CONHR<55>, -S(O)q-R<56>, -NH(CO)R<57>, -CF3, -OCF3, or -NR<27>R<28>; R<26>  = H or alkyl; R<27> and R<28> = H, alkyl, -COR<29>, or together with the N atom they form a 4-7 membered heterocycle with 1-3 heteroatoms; R<49> and R<50> = H, alkyl or alkylcarbonyl; q = 0, 1, or 2; R<56> and R<57>  = H, alkyl or alkoxy; R<29> = H, alkyl, alkoxy or -NR<30>R<31>; R<30> and R<31> = H, alkyl, or together with the N atom they form a 4-7 membered heterocycle with 1-3 heteroatoms; R<32> = H or alkyl; T' = methylene or ethylene; R<33>  = H, alkyl, - EPSILON -NR<34>R<35>, or - EPSILON -CHR<36>R<37>;  EPSILON  = 1-6C alkylene; R<34> and R<35> = H or alkyl; R<36> and R<37> = H, carbocyclic or heterocyclic aryl, (optionally substituted by alkyl, OH, halogen, NO2, alkoxy, or NR<10>R<11>); X = S or -NR<38>; R<38>  = H, alkyl, cyanoalkyl, aralkyl, alkylcarbonyl, or aralkylcarbonyl; Y' = O or S; R<1>  = H, alkyl, aminoalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, trifluoromethyl alkyl, alkenyl, allenyl, allenylalkyl, allynyl, cyanoalkyl, -(CH2)g-Z<1>R<39>, -(CH2)g-COR<40>, -(CH2)g-NHCOR<70>, aryl, aralkyl, arylcarbonyl, heteroaryl alkyl, aralkylcarbonyl, (aryl groups in these being optionally substituted by alkyl, halogen, alkoxy, nitro, CN, cyanoalkyl, amino, alkylamino, dialkylamino, -(CH2)k-Z<2>R<39> or -(CH2)k-COR<40>); and R<2> = H, alkyl, aminoalkyl, alkoxyalkyl, cycloalkyl, trifluoromethyl alkyl, -(CH2)g-NHCOR<71> (aryl and heteroaryl groups being optionally substituted by halogen, alkyl, alkoxy, OH, CN, NO2, amino, mono- or dialkylamino); or R<1> and R<2> may together form = a 3-7 membered carbocycle; Z<1> and Z<2>  = a bond, -O-, -NR<41>-, or -S-; R<39> and R<41>  = H, alkyl, alkenyl, alkynyl, or cyanoalkyl; R<40>  = H, alkyl, allenyl, allenylalkyl, alkenyl, alkynyl, cyanoalkyl, alkoxy, or -NR<42>R<43>; R<42> and R<43>  = H, alkyl, allenyl, allenylalkyl, alkenyl, alkynyl, or cyanoalkyl; R<70> and R<71>  = alkyl or alkoxy; B' = H, alkyl, -(CH2)g-Z<3>R<44>, or a carbocyclic aryl group that may be substituted 1-3 times by halogen, alkyl, alkoxy, OH, CN, NO2, amino, alkylamino, dialkylamino or carbocyclic aryl; Z<3> = bond, -O-, -NR<45>-, or -S-; R<44> and R<45>  = H, alkyl, alkenyl, alkynyl, allenyl, allenyl alkyl, or cyanoalkyl; L asterisk  = NR<46>R<47> or -OR<48>; R<46> and R<47>  = H, alkyl, cycloalkyl, alkenyl, alkynyl, allenyl, allenylalkyl, cyanoalkyl, -(CH2)g-Z<4>R<50>, -(CH2)k-COR<51>, -(CH2)k-COOR<51>, -(CH2)k-CONHR<51>, -SO2R<51>, aryl, aralkyl, aryloxyalkyl, arylcarbonyl, arylimino, aralkyl carbonyl, or heteroaryl (the aryl and heteroaryl groups being optionally substituted by halogen, alkyl, alkoxy, OH, CN, NO2, cyanoalkyl, amino, mono- or dialkylamino), -(CH2)k-Z<5>R<50>, -(CH2)k-COR<51>, or -(CH2)k-COOR<51>) or R<46> and R<47> taken together with the N atom form a 4-8 membered non-aromatic heterocycle (optionally interupted by -CH(R<53>)-, -NR<54>-, -O-, -S- or -CO); Z<4> and Z<5>  = a bond, -O-, -NR<52>- or -S-; R<50> and R<52>  = H, alkyl, alkenyl, alkynyl, allenyl, allenylalkyl, or cyanoalkyl; R<51> = H, cycloalkyl, cycloalkylalkyl, alkyl, alkenyl, alkynyl, allenyl, allenylalkyl, cyanoalkyl, alkoxyalkyl, NR<58>R<59>, aryl, or aralkyl; R<58> and R<59> = H, alkyl, alkenyl, alkynyl, allenyl, allenylalkyl, or cyanoalkyl; R<53> and R<54> = H, -(CH2)k-Z<7>R<60> or -CH2)k-COR<61>; Z<7> = a bond, -NR<62>-, or -S-; R<60> and R<62>  = H, alkyl, alkenyl, allenyl, allenyl alkyl, alkynyl, or cyanoalkyl, aryl, aralkyl, arylcarbonyl, aralkylcarbonyl, pyridinyl, pyridinylalkyl, pyridinylcarbonyl, (aryl and pyridinyl groups being optionally substituted by halogen, alkyl, alkoxy, cyanoalkyl, -(CH2)k-Z<8>R<63>,or -(CH2)k-COR<64>); R<61> = H, alkyl, allenyl, allenyl alkyl, alkenyl, alkynyl, cyanoalkyl, alkoxy or -NR<65>R<66>; R<65> and R<66> = H, alkyl, allenyl, allenyl alkyl, alkenyl, alkynyl, or cyanoalkyl; Z<8> = -O-, -S- or -NR<67>-; R<63> and R<67> = H, alkyl, allenyl, allenyl alkyl, alkenyl, alkynyl, or cyanoalkyl; R<64> = H, alkyl, allenyl alkyl, alkenyl, alkynyl, cyanoalkyl, alkoxy or -NR<68>R<69>; R<68> and R<69> = H, alkyl, allenyl, allenyl alkyl, alkenyl, alkynyl, or cyanoalkyl; R<48> = H, alkyl, alkynyl, or cyanoalkyl; g, p = 1 - 6; k, n = 0 - 6 Provisos apply, please see DEFINITIONS An Independent claim is included for the use of (III), with the proviso that when (III) is (IIIA) then A is 4-hydroxy-2,3-di-tertiary butyl phenyl, B, R<1> and R<2> are H, and L asterisk = OH, to make pharmaceutical compositions.